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PURPOSE: Orthostatic hypotension (OH) may predispose older adults to health complications leading to functional impairment. Despite the central role of the kidney in blood pressure control, the contribution of renal function in orthostatic hypotension is poorly investigated. To verify the association between Chronic Kidney Disease (CKD) and OH a population of hospitalised elderly patients with comorbidities was studied. MATERIALS AND METHODS: 174 patients were consecutively admitted to Acute Geriatric Wards. On admission, patients underwent postural systolic (SBP) and diastolic (DBP) blood pressure evaluation by automatic oscillometric device after 10 min rest in lying position, and in standing position at time 0, 1, 3 and 5 min. CKD was assumed for estimated glomerular filtration rate (e-GFR) less than 60 mL/min/1.73 m2. RESULTS: The mean age of the population enrolled was 74.4 ± 7.0. OH was found in 46.0% and CKD in 56.3% of patients, respectively. A lower e-GFR was observed in patients with (56.1 ± 16.7 mL/min/1.73 m2) than in those without OH (61.1 ± 15.9 mL/min/1.73 m2) (p < 0.05). A greater fall in SBP at 0-min (12.8 ± 6.3 vs. 7.7 ± 3.2 mmHg) and at 1-min (8.4 ± 4.5 vs. 5.7 ± 2.8 mmHg) was found in CKD patients in respect to patients without CKD during active standing test (p < 0.05). Similarly, a DBP reduction at 0-min and at 1-min was observed in CKD patients in respect to patients without CKD (p < 0.05). A multivariate logistic regression analysis showed that CKD was associated to OH (OR 2.426; 95%CI 1.192-4.937; p = 0.014). CONCLUSIONS: CKD is associated to OH in hospitalised older adults.
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Hipotensión Ortostática , Insuficiencia Renal Crónica , Humanos , Anciano , Hipotensión Ortostática/diagnóstico , Presión Sanguínea/fisiología , Insuficiencia Renal Crónica/complicaciones , Determinación de la Presión Sanguínea , RiñónRESUMEN
BACKGROUND: Idiopathic intracranial hypertension is a disease characterized by increased intracranial cerebrospinal fluid volume and pressure without evidence of other intracranial pathology. Dural sinuses are rigid structures representing a privileged low-pressure intracranial compartment. Rigidity of dural sinus ensures that the large physiologic fluctuations of cerebrospinal fluid pressure associated with postural changes or to Valsalva effect cannot be transmitted to the sinus. An abnormal dural sinus collapsibility, especially when associated with various anatomical sinus narrowing, has been proposed as a key factor in the pathogenesis of idiopathic intracranial hypertension. This pathogenetic model is based on an excessive collapsibility of the dural sinuses that leads to the triggering of a self-limiting venous collapse positive feedback-loop between the cerebrospinal fluid pressure, that compresses the sinus, and the increased dural sinus pressure upstream, that reduces the cerebrospinal fluid reabsorption rate, increasing cerebrospinal fluid volume and pressure at the expense of intracranial compliance and promoting further sinus compression. Intracranial compliance is the ability of the craniospinal space to accept small volumetric increases of one of its compartments without appreciable intracranial pressure rise. In idiopathic intracranial hypertension, a condition associated with a reduced rate of CSF reabsorption leading to its volumetric expansion, a pathologically reduced IC precedes and accompanies the rise of ICP. Syncope is defined as a transient loss of consciousness due to a transient cerebral hypoperfusion characterized by rapid onset, short duration, and spontaneous complete recovery. A transient global cerebral hypoperfusion represents the final mechanism of syncope determined by cardiac output and/or total peripheral resistance decrease. There are many causes determining low cardiac output including reflex bradycardia, arrhythmias, cardiac structural disease, inadequate venous return, and chronotropic and inotropic incompetence. Typically, syncopal transient loss of consciousness is mainly referred to an extracranial mechanism triggering a decrease in cardiac output and/or total peripheral resistance. Conversely, the association of syncope with a deranged control of intracranial compliance related to cerebral venous outflow disorders has been only anecdotally reported. CASE PRESENTATION: We report on a 57-year-old woman with daily recurrent orthostatic hypotension syncope and idiopathic intracranial hypertension-related headaches, which resolved after lumbar puncture with cerebrospinal fluid subtraction. CONCLUSIONS: A novel mechanism underlying the triggering of orthostatic syncope in the presence of intracranial hypertension-dependent reduced intracranial compliance is discussed.
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Hipertensión Intracraneal , Seudotumor Cerebral , Femenino , Humanos , Persona de Mediana Edad , Seudotumor Cerebral/complicaciones , Punción Espinal , Hipertensión Intracraneal/complicaciones , Síncope , ReflejoRESUMEN
PURPOSE: Emerging evidence suggest that infection-dependent hyperactivation of complement system (CS) may worsen COVID-19 outcome. We investigated the role of predicted high impact rare variants - referred as qualifying variants (QVs) - of CS genes in predisposing asymptomatic COVID-19 in elderly individuals, known to be more susceptible to severe disease. METHODS: Exploiting exome sequencing data and 56 CS genes, we performed a gene-based collapsing test between 164 asymptomatic subjects (aged ≥60 years) and 56,885 European individuals from the Genome Aggregation Database. We replicated this test comparing the same asymptomatic individuals with 147 hospitalized patients with COVID-19. RESULTS: We found an enrichment of QVs in 3 genes (MASP1, COLEC11, and COLEC10), which belong to the lectin pathway, in the asymptomatic cohort. Analyses of complement activity in serum showed decreased activity of lectin pathway in asymptomatic individuals with QVs. Finally, we found allelic variants associated with asymptomatic COVID-19 phenotype and with a decreased expression of MASP1, COLEC11, and COLEC10 in lung tissue. CONCLUSION: This study suggests that genetic rare variants can protect from severe COVID-19 by mitigating the activity of lectin pathway and prothrombin. The genetic data obtained through ES of 786 asymptomatic and 147 hospitalized individuals are publicly available at http://espocovid.ceinge.unina.it/.
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COVID-19 , Anciano , COVID-19/genética , Colectinas/genética , Colectinas/metabolismo , Células Germinativas , Humanos , Lectinas/genética , SARS-CoV-2 , Secuenciación del ExomaRESUMEN
AIMS: The study assesses the reliability of fr-AGILE, a validated rapid tool used for the evaluation of multidimensional frailty in older adults hospitalized with COVID-19. METHODS: Two different staff members independently assessed the presence of frailty in 144 patients aged ≥ 65 years affected by COVID-19 using the fr-AGILE tool. The internal consistency of fr-AGILE was evaluated by examining the item-total correlations and the Kuder-Richardson (KR) formula. The inter-rater reliability was evaluated using linear weighted kappa. RESULTS: Multidimensional frailty severity increases with age and is associated to higher use of non-invasive ventilation (p = 0.025), total severity score on chest tomography (p = 0.001) and in-hospital mortality (p = 0.032). Fr-AGILE showed good internal consistency (KR-20 = 0.742) and excellent inter-rater reliability (weighted kappa = 0.752 and 0.878 for frailty score and frailty degree, respectively). CONCLUSIONS: fr-AGILE tool can quickly identify and quantify multidimensional frailty in hospital settings for older patient affected by COVID-19.
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COVID-19 , Fragilidad , Anciano , Anciano Frágil , Fragilidad/diagnóstico , Evaluación Geriátrica/métodos , Hospitales , Humanos , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND: Although the prevalence of sarcopenic obesity is increasing, nowadays a universally accepted definition still does not exist. Because, this clinical entity is defined as the combination of obesity and sarcopenia, the diagnosis appears to be strictly linked to criteria used for sarcopenia and the available prevalence data are not uniform. To investigate the prevalence of sarcopenic obesity in older persons according to EWGSOP2 and FNIH criteria. Second, to evaluate the prevalence of diabetes in patients with sarcopenia diagnosed by the two definitions. METHODS: Observational multicenter study performed in 2014 on older patients admitted to 12 Italian hospitals (GLISTEN Study). Data were collected through standardized questionnaires, which assessed: socio-demographic data, cognitive status, functional abilities, pharmacological therapy, comorbidities, and blood tests. Moreover, muscle mass and strength and physical performance were evaluated. RESULTS: Six hundred and ten were included in the analyses. Among sarcopenic patients, the prevalence of sarcopenic obesity was 30.8% with FNIH and 0% with EWGSOP2 criteria. According to EWGSOP2 criteria, 23.7% of sarcopenic and 30.8% of non-sarcopenic patients were affected by diabetes (p = 0.101); otherwise, using FNIH criteria, 36.3% of sarcopenic and 26.9% of non-sarcopenic patients were diabetic (p = 0.030). After adjustment for potential confounders, diabetic patients had a 73% higher probability of being sarcopenic according to FNIH criteria (OR 1.73; 95% CI 1.13-2.64). CONCLUSIONS: The EWGSOP2 and FNIH sarcopenia criteria are differently related to the prevalence of obesity and diabetes. The EWGSOP2 criteria seem to be not suitable to identify people with sarcopenic obesity.
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Diabetes Mellitus , Sarcopenia , Anciano , Anciano de 80 o más Años , Diabetes Mellitus/epidemiología , Fuerza de la Mano , Humanos , Obesidad/epidemiología , Prevalencia , Sarcopenia/epidemiologíaRESUMEN
PURPOSE OF REVIEW: Immune checkpoint inhibitors, such as monoclonal antibodies targeting CTLA-4, PD-1, and PD-L1, have improved the outcome of many malignancies, but serious immune-related cardiovascular adverse events have been observed. Patients' risk factors for these toxicities are currently being investigated. RECENT FINDINGS: Interfering with the CTLA-4 and PD-1 axes can bring to several immune-related adverse events, including cardiotoxic events such as autoimmune myocarditis, pericarditis, and vasculitis, suggesting that these molecules play an important role in preventing autoimmunity. Risk factors (such as pre-existing cardiovascular conditions, previous and concomitant cardiotoxic treatments, underlying autoimmune diseases, tumor-related factors, simultaneous immune-related toxic effects, and genetic factors) should be always recognized for the correct management of these toxicities.
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Cardiotoxicidad/etiología , Puntos de Control del Ciclo Celular/efectos de los fármacos , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Inmunoterapia/efectos adversos , Antineoplásicos Inmunológicos/uso terapéutico , Antígeno B7-H1 , Antígeno CTLA-4 , Humanos , Neoplasias/tratamiento farmacológico , Factores de RiesgoRESUMEN
Genome-wide association studies (GWAS) found locus 3p21.31 associated with severe COVID-19. CCR5 resides at the same locus and, given its known biological role in other infection diseases, we investigated if common noncoding and rare coding variants, affecting CCR5, can predispose to severe COVID-19. We combined single nucleotide polymorphisms (SNPs) that met the suggestive significance level (P ≤ 1 × 10-5) at the 3p21.31 locus in public GWAS datasets (6406 COVID-19 hospitalized patients and 902,088 controls) with gene expression data from 208 lung tissues, Hi-C, and Chip-seq data. Through whole exome sequencing (WES), we explored rare coding variants in 147 severe COVID-19 patients. We identified three SNPs (rs9845542, rs12639314, and rs35951367) associated with severe COVID-19 whose risk alleles correlated with low CCR5 expression in lung tissues. The rs35951367 resided in a CTFC binding site that interacts with CCR5 gene in lung tissues and was confirmed to be associated with severe COVID-19 in two independent datasets. We also identified a rare coding variant (rs34418657) associated with the risk of developing severe COVID-19. Our results suggest a biological role of CCR5 in the progression of COVID-19 as common and rare genetic variants can increase the risk of developing severe COVID-19 by affecting the functions of CCR5.
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COVID-19/genética , COVID-19/metabolismo , Predisposición Genética a la Enfermedad , Receptores CCR5/genética , Receptores CCR5/metabolismo , Alelos , Bronquios/metabolismo , Bronquios/patología , Bronquios/virología , COVID-19/fisiopatología , Cromosomas Humanos/genética , Estudios de Cohortes , Biología Computacional , Bases de Datos Genéticas , Estudio de Asociación del Genoma Completo , Genotipo , Humanos , Pulmón/metabolismo , Pulmón/patología , Pulmón/virología , Polimorfismo de Nucleótido Simple , Secuenciación del ExomaRESUMEN
BACKGROUND: Several tools have been proposed and validated to operationally define frailty. Recently, the Italian Frailty index (IFi), an Italian modified version of Frailty index, has been validated but its use in clinical practice is limited by long time of administration. Therefore, the aim of this study was to create and validate a quick version of the IFi (AGILE). METHODS: Validation study was performed by administering IFi and AGILE, after a Comprehensive Geriatric Assessment (CGA) in 401 subjects aged 65 or over (77 ± 7 years). AGILE was a 10-items tool created starting from the more predictive items of the four domains of frailty investigated by IFi (mental, physical, socioeconomic and nutritional). AGILE scores were stratified in light, moderate and severe frailty. At 24 months of follow-up, death, disability (taking into account an increase in ADL lost ≥1 from the baseline) and hospitalization were considered. Area under curve (AUC) was evaluated for both IFi and AGILE. RESULTS: Administration time was 9.5 ± 3.8 min for IFi administered after a CGA, and 2.4 ± 1.2 min for AGILE, regardless of CGA (p < 0.001). With increasing degree of frailty, prevalence of mortality increased progressively from 6.5 to 41.8% and from 9.0 to 33.3%, disability from 16.1 to 64.2% and from 22.1 to 59.8% and hospitalization from 17.2 to 58.7% and from 27.0 to 52.2% with AGILE and IFi, respectively (p = NS). Relative Risk for each unit of increase in AGILE was 56, 44 and 24% for mortality, disability and hospitalization, respectively and was lower for IFi (8, 7 and 4% for mortality, disability and hospitalization, respectively). The AUC was higher in AGILE vs. IFi for mortality (0.729 vs. 0.698), disability (0.715 vs. 0.682) and hospitalization (0.645 vs. 0.630). CONCLUSIONS: Our study shows that AGILE is a rapid and effective tool for screening multidimensional frailty, able to predict mortality, disability and hospitalization, especially useful in care settings that require reliable assessment instruments with short administration time.
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Fragilidad , Anciano , Anciano de 80 o más Años , Anciano Frágil , Fragilidad/diagnóstico , Evaluación Geriátrica , Humanos , Italia/epidemiología , Estudios ProspectivosRESUMEN
Type 2 myocardial infarctions (T2-MI) is a type of necrosis that results from reduced oxygen supply and/or increased demand secondary to other causes unrelated to acute coronary atherothrombosis. The development and implementation of sensitive and high-sensitivity cardiac necrosis marker and the age-related increase of comorbidity lead to a boost of the frequency of T2-MI. T2-MI is often a complication of a high degree of clinical frailty in older adults, emerging as a "geriatric syndrome". Age-related non-cardiovascular causes may be the triggering factors and are strongly associated with the diagnosis, treatment, and prognosis of T2-MI. To date, there are no guidelines on management of this pathology in advancing age. Patient-centered approach and comprehensive geriatric assessment play a key role in the diagnosis, therapy and prognosis of geriatric patients with T2-MI.
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Envejecimiento , Infarto del Miocardio/diagnóstico , Anciano , Comorbilidad , Evaluación Geriátrica , Humanos , Infarto del Miocardio/epidemiología , Necrosis , PronósticoRESUMEN
OBJECTIVE: The aims of the present study were: (a) to obtain new normative data of the Italian version of the Mini-Mental Examination State (MMSE) (Measso et al. in Dev Neuropsychol 9:77-85, 1993) by administering the tool to a sample of normal Italian individuals more representative of the current Italian population; (b) to compare the sensitivity of this tool in detecting patients suffering from Alzheimer's disease (AD according to NIA-AA), as compared to the those reported in previous normative Italian studies. METHODS: MMSE was administered to 314 normal subjects recruited among individuals (and/or their relatives) attending the Offices of General Practitioners (GP) or Memory Clinics in Campania (Italy) by convenience sampling. A group of 47 patients with AD were included into the study. The effect of demographic variables on the raw MMSE scores of normal subjects was checked by multiple linear regression assuming MMSE scores as dependent variable and age, gender and education as the independent one(s). Therefore, a simultaneous regression model was constructed to correct the raw scores according the sensitive variables. Correction grid and equivalent scores were devised to classify subject's performance. RESULTS: The mean raw MMSE score was 27.78 (SD = 1.80) (range 22-30/30). There was no significant difference between scores achieved by men or women (p = 0.688). Multiple linear regression analysis showed a significant effect of age and years of school attendance on the MMSE raw score, whereas gender did not show any significant effect. The cutoff score, distinguishing between pathological and normal performances, was fixed at the fifth centile corresponding to 24.9/30, higher than the current score of 23.8/30. The new cutoff value was able to identify 44/47 patients with AD, in contrast to 38/47 subjects detected by currently used norms. CONCLUSIONS: (1) A more updated and representative population sample; (2) a new cutoff threshold able to distinguish between normal and pathological performances; (3) a correction grid that reduces the risk of false-positive and false-negative values due to the influence of the main demographic factors; (4) greater sensitivity, compared to previous Italian normative studies in identifying people with dementia.
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Pruebas de Estado Mental y Demencia , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/diagnóstico , Femenino , Humanos , Italia , Modelos Lineales , Masculino , Memoria , Persona de Mediana Edad , Análisis MultivarianteRESUMEN
Systemic sclerosis is an auto-immune disease characterized by skin involvement that often affects multiple organ systems. Pulmonary hypertension is a common finding that can significantly impact prognosis. Molecular pathophysiological mechanisms underlying pulmonary hypertension in systemic sclerosis can be extremely heterogeneous, leading to distinct clinical phenotypes. In addition, different causes of pulmonary hypertension may overlap within the same patient. Since pulmonary hypertension treatment is very different for each phenotype, it is fundamental to perform an adequate diagnostic work-up to properly and promptly identify the prevalent mechanism underlying pulmonary hypertension in order to start the right therapies. When pulmonary hypertension is caused by a primary vasculopathy of the small pulmonary arteries, treatment with pulmonary vasodilators, often in an initial double-combination regimen, is indicated, aimed at reducing the mortality risk profile. In this review, we describe the different clinical phenotypes of pulmonary hypertension in the scleroderma population and discuss the utility of clinical tools to identify the presence of pulmonary vascular disease. Furthermore, we focus on systemic sclerosis-associated pulmonary arterial hypertension, highlighting the advances in the knowledge of right ventricular dysfunction in this setting and the latest updates in terms of treatment with pulmonary vasodilator drugs.
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Hipertensión Pulmonar/diagnóstico , Esclerodermia Sistémica/complicaciones , Vasodilatadores/uso terapéutico , Humanos , Hipertensión Pulmonar/tratamiento farmacológico , Hipertensión Pulmonar/etiología , Fenotipo , Pronóstico , Factores de RiesgoRESUMEN
BACKGROUND AND AIM: Permanent Atrial Fibrillation (pAF) is associated with increased risk of embolic complications. The relationship between pAF and pulmonary embolism (PE) has not been extensively investigated in elderly patients. Here, we aim at verifying whether pAF is associated to an increased risk of PE in a cohort of elderly patients with and without Deep Vein Thrombosis (DVT). METHODS: 235 patients older than 65 years with PE with or without pAF were retrospectively enrolled and stratified by the absence or presence of DVT. The diagnosis of PE was performed by computed tomography angiography (CTA). Right echocardiographic parameters were monitored. The severity of PE was evaluated by CTA quantization (PE score = 1, involvement of main branches of pulmonary artery) and by dimer-D (> 3000 µg/L). RESULTS: DVT was identified only in 51 cases of PE (21.7%). pAF prevalence was higher in PE without than in those with DVT (64.9% vs. 35.1%, p < 0.01). PE severity was more evident in pAF patients without than in those with DVT. Multivariate analysis of the role of pAF on PE severity confirms these results (RR = 3.41 for PE score = 1, and 8.55 for dimer-D > 3000 µg/L). CONCLUSIONS: We conclude that in elderly patients with PE, the prevalence of pFA was doubled, in the absence of DVT, and it is associated with a more severe PE in the absence than in the presence of DVT. Thus, in the absence of DVT, pFA should be considered as cause of PE.
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Fibrilación Atrial/complicaciones , Embolia Pulmonar/complicaciones , Anciano , Anciano de 80 o más Años , Fibrilación Atrial/diagnóstico por imagen , Estudios de Cohortes , Angiografía por Tomografía Computarizada , Femenino , Humanos , Masculino , Análisis Multivariante , Prevalencia , Embolia Pulmonar/diagnóstico por imagen , Estudios Retrospectivos , Factores de Riesgo , Trombosis de la VenaRESUMEN
BACKGROUND: Recently the Berlin Aging Study II (BASE-II) showed that polypharmacy is associated with clinically relevant sarcopenia among community-dwelling older persons. Here we report findings from the GLISTEN study about the association of polypharmacy with sarcopenia among older medical in-patients. METHODS: The GLISTEN study investigated prevalence and clinical correlates of sarcopenia in older patients admitted to geriatric and internal medicine acute care wards of 12 Italian hospitals. RESULTS: In this sample of older medical in-patients with high prevalence of sarcopenia (34.7%) and polypharmacy (70.2%) we did not observe a significant association of polypharmacy with sarcopenia. CONCLUSIONS: Present findings demonstrate that the association of polypharmacy with sarcopenia, observed in the BASE-II study, is not evident in the GLISTEN sample, being our patients significantly older, more multi-morbid, with high prevalence of sarcopenia and polypharmacy, suggesting that this association might vary according to the heterogeneous health, functional, and nutritional characteristics of older people.
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Evaluación Geriátrica , Polifarmacia , Sarcopenia/epidemiología , Anciano , Anciano de 80 o más Años , Estudios Transversales , Femenino , Humanos , Vida Independiente/estadística & datos numéricos , Italia , Masculino , Prevalencia , Factores de Riesgo , Sarcopenia/etiologíaRESUMEN
OBJECTIVE: To devise an Italian version of the quick mild cognitive impairment screen (Qmci) and to obtain normative data. METHODS: An Italian version of the Qmci screen (Qmci-I) was administered to 307 subjects free from cognitive impairment. The normative sample was divided into three age levels (50-59; 60-69 and 70-80 years) and four education levels (3-5; 6-8; 9-13; >13 years of school attendance). Multiple regression analyses were used to evaluate the effect of age, sex and schooling on Qmci-I scores (overall and by domains) and to calculate cut-off values, with reference to the confidence interval on the fifth centile. RESULTS: The mean Qmci-I score was 64/100 (SD = 11). The age variable showed a significant negative effect on the overall Qmci-I score, with older people performing worse than younger ones. Conversely, education was associated with higher scores. Significant effects of age and education affected logical memory alone. For the other domains, the following effects were found: (1) higher age associated with lower scores on delayed recall; (2) higher education levels associated with higher scores on immediate recall, clock drawing and word fluency. The adjusted cut-off score for the Qmci-I screen in this sample was 49.4. Qmci-I scores were weakly correlated with those of MMSE (rho = 0.20). CONCLUSIONS: The Qmci-I is a rapid and multi-domain short cognitive screening instrument useful for evaluating cognitive functions. However, like other screening tools, it is significantly influenced by age and education, requiring normative data and correction of values when used in the clinical practice.
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Disfunción Cognitiva/diagnóstico , Pruebas Neuropsicológicas , Anciano , Anciano de 80 o más Años , Cognición , Disfunción Cognitiva/psicología , Femenino , Humanos , Italia , Lenguaje , Masculino , Pruebas de Estado Mental y Demencia , Persona de Mediana EdadRESUMEN
Sirtuins (SIRTs) are seven nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylases enzymes (SIRT1-7) that play an important role in maintaining cellular homeostasis. Among those, the most studied are SIRT1 and SIRT3, a nuclear SIRT and a mitochondrial SIRT, respectively, which significantly impact with an increase in mammals' lifespan by modulating metabolic cellular processes. Particularly, when activated, both SIRT1 and 3 enhance pancreatic ß-cells' insulin release and reduce inflammation and oxidative stress pancreatic damage, maintaining then glucose homeostasis. Therefore, SIRT1 and 3 activators have been proposed to prevent and counteract metabolic age-related diseases, such as type 2 diabetes mellitus (T2DM). Physical activity (PA) has a well-established beneficial effect on phenotypes of aging like ß-cell dysfunction and diabetes mellitus. Recent experimental and clinical evidence reports that PA increases the expression levels of both SIRT1 and 3, suggesting that PA may exert its healthy contribute even by activating SIRTs. Therefore, in the present article, we discuss the role of SIRT1, SIRT3, and PA on ß-cell function and on diabetes. We also discuss the possible interaction between PA and activation of SIRTs as a possible therapeutic strategy to maintain glucose hemostasis and to prevent T2DM and its complications, especially in the elderly population.
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Glucosa/metabolismo , Homeostasis , Sirtuina 1/química , Sirtuina 3/química , Animales , Diabetes Mellitus Tipo 2/etiología , Diabetes Mellitus Tipo 2/metabolismo , Susceptibilidad a Enfermedades , Ejercicio Físico , Humanos , Células Secretoras de Insulina/metabolismo , Enfermedades Metabólicas/etiología , Enfermedades Metabólicas/metabolismo , Sirtuina 1/metabolismo , Sirtuina 3/metabolismoRESUMEN
Neurodegenerative diseases are among the leading causes of mortality and disability worldwide. However, current therapeutic approaches have failed to reach significant results in their prevention and cure. Protein Kinase Cs (PKCs) are kinases involved in the pathophysiology of neurodegenerative diseases, such as Alzheimer's Disease (AD) and cerebral ischemia. Specifically ε, δ, and γPKC are associated with the endogenous mechanism of protection referred to as ischemic preconditioning (IPC). Existing modulators of PKCs, in particular of εPKC, such as ψεReceptor for Activated C-Kinase (ψεRACK) and Resveratrol, have been proposed as a potential therapeutic strategy for cerebrovascular and cognitive diseases. PKCs change in expression during aging, which likely suggests their association with IPC-induced reduction against ischemia and increase of neuronal loss occurring in senescent brain. This review describes the link between PKCs and cerebrovascular and cognitive disorders, and proposes PKCs modulators as innovative candidates for their treatment. We report original data showing εPKC reduction in levels and activity in the hippocampus of old compared to young rats and a reduction in the levels of δPKC and γPKC in old hippocampus, without a change in their activity. These data, integrated with other findings discussed in this review, demonstrate that PKCs modulators may have potential to restore age-related reduction of endogenous mechanisms of protection against neurodegeneration.
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Encéfalo/metabolismo , Neuroprotección , Proteína Quinasa C/metabolismo , Factores de Edad , Envejecimiento/metabolismo , Animales , Biomarcadores , Susceptibilidad a Enfermedades , Desarrollo de Medicamentos , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Terapia Molecular Dirigida , Enfermedades del Sistema Nervioso/diagnóstico , Enfermedades del Sistema Nervioso/tratamiento farmacológico , Enfermedades del Sistema Nervioso/etiología , Enfermedades del Sistema Nervioso/metabolismo , Proteína Quinasa C/química , Proteína Quinasa C/genética , Transducción de Señal/efectos de los fármacosRESUMEN
Traditional risk factors of cardiovascular death in the general population, including body mass index (BMI), serum cholesterol, and blood pressure are also found to relate to outcomes in the geriatric population, but in a differing direction. A higher body mass index, hypercholesterolemia and hypertension are not harmful but even permit better survival at advancing age. This phenomenon is called "reverse epidemiology" or "risk factor paradox" and is also detected in a variety of chronic disease states such as chronic heart failure. Accordingly, a low BMI, blood pressure and cholesterol values are associated with a worse prognosis. Several possible causes are hypothesized to explain this elderly paradox, but this phenomenon remains controversial and its underlying reasons are poorly understood. The aim of this review is to recognize the factors behind this intriguing phenomenon and analyse the consequences that it can bring in the management of the cardiovascular therapy in elderly patient. Finally, a new phenotype identified as "catabolic syndrome" has been postulated.
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Enfermedades Cardiovasculares/etiología , Insuficiencia Cardíaca/etiología , Síndrome Metabólico/complicaciones , Anciano , Presión Sanguínea , Índice de Masa Corporal , Colesterol/sangre , Enfermedad Crónica , Humanos , Hipertensión/complicaciones , Factores de Riesgo , Pérdida de PesoRESUMEN
The traditional model of care is based on "disease-centered" management that requires the organization of the hospital in specialized wards, to which the patient is assigned for the main disease. The growing need to optimize economical and human resources and to promote a global approach to the patient has led to the setting up of the intensity of care model. It is a health system based on a "patient-centered" approach, where the hospital is organized in departments dedicated to patients with homogenous needs of care. In Italy, intensity of care model is currently being tested in the hospital organization, where three levels of intensity are proposed: low, medium and high. The purpose of the following review is to describe the role and importance of the Geriatrician in each of these care settings and to highlight the contradiction of a National Health System which promotes the geriatric approach to all types of patients, but does not invest in the formation and integration of the figure of the Geriatrician in clinical practice, condemning it to marginalization or even extinction.
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Geriatras/organización & administración , Atención Dirigida al Paciente/organización & administración , Hospitales , Humanos , ItaliaRESUMEN
BACKGROUND: Differential diagnosis between syncope and epilepsy in patients with transient loss of consciousness of uncertain etiology is still unclear. Thus, the aim of the present work is to evaluate the prevalence of syncope in patients with "possible" or "drug-resistant" epilepsy. METHODS: The Overlap between Epilepsy and SYncope Study (OESYS) is a multicenter prospective observational study designed to estimate the prevalence of syncope in patients followed in Epilepsy Centers for "possible" or "drug-resistant" epilepsy and assessed according the European Society of Cardiology (ESC) guidelines of syncope diagnosis. RESULTS: One hundred seven patients were evaluated; 63 (58.9%) had possible and 44 (41.1%) drug-resistant epilepsy. A final diagnosis of isolated syncope was in 45 patients (42.1%), all with possible epilepsy (45/63, 71.4%). Isolated epilepsy was found in 21 patients (19.6%) and it was more frequent in the drug-resistant than in the possible epilepsy group (34.1% vs. 9.5%, p = 0.002). More importantly, syncope and epilepsy coexisted in 37.4% of all patients but the coexistence was more frequent among patients with drug-resistant than possible epilepsy (65.9% vs. 17.5%, p < 0.001). CONCLUSIONS: Isolated syncope was diagnosed in ≈ 70% of patients with possible epilepsy. Syncope and epilepsy coexisted in ≈ 20% of patients with possible and in ≈ 60% of patients with drug-resistant epilepsy. These findings highlight the need of ESC guidelines of syncope approach in patients with possible and drug-resistant epilepsy.
Asunto(s)
Epilepsia/diagnóstico , Síncope/diagnóstico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Síncope/etiología , Adulto JovenRESUMEN
BACKGROUND AND AIM: Several measurements were taken for frailty classification in geriatric population. "Frailty index" is based on "deficits in health," but it is still not available in Italian version. Thus, the aim of the present work was to validate a version of "frailty index" for the Italian geriatric community. METHODS: The validation of Italian frailty index (IFi) is based on a cohort study that enrolled 1077 non-disabled outpatients aged 65 years or older (81.3 ± 6.5 years) in Naples (Italy). IFi has been expressed as a ratio of deficits present/deficits considered after a comprehensive geriatric assessment. IFi was stratified in light, moderate and severe frailty. Mortality, disability (considering an increase in ADL lost ≥1 from the baseline) and hospitalization were considered at 3, 6, 12, 18 and 24 months of follow-up. Area under curve (AUC) was evaluated for both Fried's and IFi frailty index. RESULT: At the end of follow-up, mortality increased from 1.0 to 30.3%, disability from 40.9 to 92.3% and hospitalization from 0.0 to 59.0% (p < 0.001 for trend). Multivariate analysis shows that the relative risk for unit increase in IFi is 1.09 (95% CI = 1.01-1.17, p = 0.013) for mortality, 1.04 (95% CI = 1.01-1.06, p = 0.024) for disability and 1.03 (95% CI = 1.01-1.07, p = 0.041) for hospitalization. AUC is higher in IFi with respect to Fried's frailty index when considering mortality (0.809 vs. 0.658, respectively), disability (0.800 vs. 0.729, respectively) and hospitalization (0.707 vs. 0.646, respectively). CONCLUSIONS: IFi is a valid measure of frailty after the comprehensive geriatric assessment in an Italian cohort of non-institutionalized patients.